Quantitative levonorgestrel plasma level measurements in patients with regular and prolonged use of the levonorgestrel-releasing intrauterine system.

BACKGROUND: The levonorgestrel-releasing intrauterine system (LNG-IUS) is well accepted as an easy-to-use contraceptive with an excellent side-effect profile. It contains a reservoir of 52 mg of levonorgestrel (LNG) with continuous release of the steroid. Its contraceptive use is approved for 5 years. The aim of this study was to determine the plasma concentration of LNG and its variation with time in patients with in-dwelling LNG-IUS Mirena®. STUDY DESIGN: In this study, we determined LNG plasma concentrations in 110 women with LNG-IUS at different time points of use. Time from insertion of the system in the study population ranged from 20 days to 11.1 years. Quantitative LNG levels were determined using a validated liquid chromatography-tandem mass spectrometry assay. RESULTS: The mean±SD LNG plasma level in all women was 147±59 pg/mL. A highly significant negative correlation between LNG plasma level and LNG-IUS time of use could be demonstrated. In the first year of use, LNG plasma level was as high as 191±71 pg/mL, decreasing to 157±68 pg/mL in the second year and 134±41 pg/mL in the third year. Even after exceeding the recommended period of LNG-IUS use, systemic LNG concentrations were detectable: 133±38 pg/mL in the sixth year, 133±48 pg/mL in the seventh year and 117±45 pg/mL in the eighth year. Furthermore, a significant negative correlation between LNG plasma level and body mass index could be shown. CONCLUSION: Systemic LNG concentrations can be found in all patients with LNG-IUS IUS. However, concentrations are much lower than in other forms of LNG application. Moreover, this study demonstrates that a systemic effect of LNG-IUS can also be found after the recommended contraceptive lifespan of 5 years.